A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV‐positive patients

Busti, Anthony J.; Tsikouris, James P.; Peeters, Michael J.; Das, Sandeep R; Canham, Russell M.; Abdullah, Shuaib; Margolis, David M.

doi:10.1111/j.1468-1293.2006.00382.x

Cited by 44 publications

(67 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ATV has a peak free concentration of 0.18-1.06 μmol/L, which is less than the IC 50 value of 5.7±1.8 μmol/L obtained in our results. This result could explain the lack of a significant influence of PI on QTc prolongation, which is consistent with the recent data showing that ATV has no effect on ventricular repolarization with repeated administration [11] .…”

Section: Discussionsupporting

confidence: 81%

“…Similar to other PIs [4][5][6][7] , ATV has previously been reported to be specifically associated with acquired long-QT syndrome, druginduced QT prolongation, and torsades de pointes (TdP) in HIV-infected patients [8][9][10] . However, these results contradict other recently published studies [11,12].…”

Section: Introductioncontrasting

confidence: 57%

“…In addition, there has also been a report of QT interval prolongation or the risk of ventricular tachycardia (VT) with combined treatment using ATV and other drugs such as methadone [9] . Recently, it was reported that ATV did not prolong the QTc interval and did not increase QTc dispersion [11] . Charbit et al [12] studied the relationship between PIs and QT interval prolongation in patients with AIDS and showed that PIs inhibit the hERG current in vitro but are not determinant or independent factors of QT prolongation in patients with AIDS.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The protease inhibitor atazanavir blocks hERG K+ channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane

et al. 2015

View full text Add to dashboard Cite

Aim: Atazanavir (ATV) is a HIV-1 protease inhibitor for the treatment of AIDS patients, which is recently reported to provoke excessive prolongation of the QT interval and torsades de pointes (TdP). In order to elucidate its arrhythmogenic mechanisms, we investigated the effects of ATV on the hERG K + channels expressed in HEK293 cells. Methods: hERG K + currents were detected using whole-cell patch clamp recording in HEK293 cells transfected with EGFP-hERG plasmids. The expression of hERG protein was measured with Western blotting. Two mutants (Y652A and F656C) were constructed in the S6 domain within the inner helices of hERG K + channels that were responsible for binding of various drugs. The trafficking of hERG protein was studied with confocal microscopy. Results: Application of ATV (0.01-30 μmol/L) concentration-dependently decreased hERG K + currents with an IC 50 of 5.7±1.8 μmol/L. ATV (10 μmol/L) did not affect the activation and steady-state inactivation of hERG K + currents. Compared with the wild type hERG K + channels, both Y652A and F656C mutants significantly reduced the inhibition of ATV on hERG K + currents. Overnight treatment with ATV (0.1-30 μmol/L) concentration-dependently reduced the amount of fully glycosylated 155 kDa hERG protein without significantly affecting the core-glycosylated 135 kDa hERG protein in the cells expressing the WT-hERG protein. Confocal microscopy studies confirmed that overnight treatment with ATV obstructed the trafficking of hERG protein to the cell membrane. Conclusion: ATV directly blocks hERG K + channels via binding to the residues Y652 and F656 in the S6 domain, and indirectly obstructs the transport of the hERG protein to the cell membrane.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Introductioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The protease inhibitor atazanavir blocks hERG K+ channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In the present study, no 24-h sympathetic enhancement was observed in any group. Although it has been shown that antiretroviral drugs do not affect the QT or QTc intervals (40), as also found in the present findings, further studies monitoring QT interval adaptation are warranted as new drugs appear on this scenario.…”

Section: Discussionmentioning

confidence: 43%

Circadian cardiac autonomic function in perinatally HIV-infected preschool children

Benchimol-Barbosa

2009

Braz J Med Biol Res

View full text Add to dashboard Cite

The 24-h heart rate variability and QT-interval adaptation was investigated in perinatally HIV-infected preschool children classified according to immunological status in order to assess autonomic function at early stages of infection. Thirty-five perinatally HIV-infected and clinically stable children (4.8 ± 0.3 years) were enrolled after approval of the study by the University Hospital Pedro Ernesto Ethics Committee and written informed parental consent was obtained. The children were classified according to peripheral CD4+ count (cells/µL) as follows: group 1, N = 11 (≥1000); group 2, N = 7 (≥500 and <1000); group 3, N = 17 (<500). Left ventricular ejection fraction (>55%), 24-h RR interval variability (RRV) indexes (NN, SDANN, SDNN index, r-MSSD) and 24-h QT and Bazett-corrected QT (QTc) were determined, and groups were matched for age, body surface area, and left ventricular ejection fraction, reducing biases in RRV. The peak differences (∆) between the highest and lowest RRV and QT indexes were extracted from nocturnal (1 am-6 am) and daytime (1 pm-6 pm) hourly assessed segments, respectively. Pearson’s correlation (r) and Kruskal-Wallis ANOVA were used to compare groups. CD4+ count correlated positively with ∆NN (r = 0.45; P = 0.003). There were no significant differences in daytime NN among groups. Nighttime SDNN index (P = 0.01), nighttime r-MSSD (P = 0.003), ∆NN (P = 0.01), ∆SDNN index (P = 0.03) and ∆r-MSSD (P = 0.004) were significantly lower in group 3 than in the other groups. Expected nighttime QTc-interval lengthening was not observed in all groups. In perinatally HIV-infected preschool children with preserved left ventricular systolic function, parasympathetic-mediated autonomic dysfunction parallels immune status, impairing both RRV and circadian QTc interval adaptation

show abstract

“…O uso do ATV na terapia antirretroviral também foi associado ao bloqueio atrioventricular de primeiro grau 14 .…”

Section: Discussionunclassified

Efeitos adversos da profilaxia antirretroviral após exposição ocupacional ao HIV

Alverca¹,

Quixabeiro²,

Martins³

2018

Rev. Bras. Med. Trab.

View full text Add to dashboard Cite

RELATO DE CASORESUMO | A exposição ocupacional a material biológico com risco de transmissão do vírus da imunodeficiência humana (HIV) constitui uma emergência médica. A profilaxia pós-exposição (PEP) deve ser iniciada precocemente e mantida por 28 dias. Desde julho de 2015, o Ministério da Saúde passou a recomendar o uso combinado de três drogas antirretrovirais para a PEP, menos tóxicas e melhor toleradas do que as usadas anteriormente. Apesar disso, quase metade dos expostos em uso da PEP apresenta efeitos adversos. Geralmente, eles são leves e autolimitados. Os mais comuns são alterações gastrointestinais, astenia, cefaleia e tontura. Entretanto, eventos mais graves já foram observados e a taxa de interrupção da profilaxia permanece elevada. Em 2017, o Ministério da Saúde modificou o esquema de primeira linha da PEP, substituindo o terceiro antirretroviral. Esse artigo relata um caso de toxicidade associada ao uso da PEP após exposição ocupacional a material biológico contaminado pelo HIV, traz a revisão dos potenciais efeitos adversos das drogas antirretrovirais que compõem o esquema profilático preconizado pelo Ministério da Saúde e discute a conduta do médico do trabalho diante dessas complicações. Palavras-chave | exposição ocupacional; profilaxia pós-exposição; efeitos colaterais e reações adversas relacionados a medicamentos; antirretrovirais.ABSTRACT | Occupational exposure to biological materials involving risk of human immunodeficiency virus (HIV) transmission is a medical emergency. Post-exposure prophylaxis (PEP) should be started early and administered for 28 days. Since July 2015, the Brazilian Ministry of Health recommends the combined use of three antiretroviral drugs for PEP, which are less toxic and better tolerated than the ones previously used. Nevertheless, almost half of the exposed individuals under PEP exhibit adverse effects, which are usually mild and self-limited. The most frequent adverse events are gastrointestinal disorders, asthenia, headache and dizziness. However, more severe events have been reported, and the rate of non-completion of prophylaxis remains high. In 2017, the Brazilian Ministry of Health modified the first-line PEP regimen involving replacement of the third antiretroviral drug. The present article reports a case of toxicity associated with PEP following an occupational accident involving exposure to HIV infected biological material. In addition, we review the potential adverse effects of antiretroviral drugs included in the prophylactic regimens recommended by the Brazilian Ministry of Health and discuss measures occupational physicians should adopt vis-à-vis these complications.

show abstract

A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV‐positive patients

Cited by 44 publications

References 31 publications

The protease inhibitor atazanavir blocks hERG K+ channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane

The protease inhibitor atazanavir blocks hERG K+ channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane

Circadian cardiac autonomic function in perinatally HIV-infected preschool children

Efeitos adversos da profilaxia antirretroviral após exposição ocupacional ao HIV

Contact Info

Product

Resources

About